Stability of Simple Periodic Orbits and Chaos in a Fermi -- Pasta -- Ulam Lattice

We investigate the connection between local and global dynamics in the Fermi -- Pasta -- Ulam (FPU) $\beta$ -- model from the point of view of stability of its simplest periodic orbits (SPOs). In particular, we show that there is a relatively high $q$ mode $(q=2(N+1)/{3})$ of the linear lattice, having one particle fixed every two oppositely moving ones (called SPO2 here), which can be exactly continued to the nonlinear case for $N=5+3m, m=0,1,2,...$ and whose first destabilization, $E_{2u}$, as the energy (or $\beta$) increases for {\it any} fixed $N$, practically {\it coincides} with the onset of a ``weak'' form of chaos preceding the break down of FPU recurrences, as predicted recently in a similar study of the continuation of a very low ($q=3$) mode of the corresponding linear chain. This energy threshold per particle behaves like $\frac{E_{2u}}{N}\propto N^{-2}$. We also follow exactly the properties of another SPO (with $q=(N+1)/{2}$) in which fixed and moving particles are interchanged (called SPO1 here) and which destabilizes at higher energies than SPO2, since $\frac{E_{1u}}{N}\propto N^{-1}$. We find that, immediately after their first destabilization, these SPOs have different (positive) Lyapunov spectra in their vicinity. However, as the energy increases further (at fixed $N$), these spectra converge to {\it the same} exponentially decreasing function, thus providing strong evidence that the chaotic regions around SPO1 and SPO2 have ``merged'' and large scale chaos has spread throughout the lattice.Comment: Physical Review E, 18 pages, 6 figure

Effects of small interfering RNA targeting thymidylate synthase on survival of ACC3 cells from salivary adenoid cystic carcinoma

<p>Abstract</p> <p>Background</p> <p>Thymidylate synthase (TS) is an important target for chemotherapeutic treatment of cancer and high expression of TS has been associated with poor prognosis or refractory disease in several cancers including colorectal and head and neck cancer. Although TS is known to regulate cell cycles and transcription factors, its potency as a therapeutic target has not been fully explored in adenoid cystic carcinoma (ACC).</p> <p>Methods</p> <p>An ACC cell line (ACC3) was transfected with siRNA targeting the TS gene and inhibition of cell growth and induction of apoptosis-associated molecules were evaluated <it>in vitro</it>. In addition, the <it>in vivo </it>effect of TS siRNA on tumor progression was assessed using a xenograft model.</p> <p>Results</p> <p>Our results demonstrated that ACC3 cells showed significantly higher TS expression than non-cancer cell lines and the induction of TS siRNA led to inhibition of cell proliferation. The effect was associated with an increase in p53, p21, and active caspase-3 and S-phase accumulation. We also found up-regulation of spermidine/spermine N1-acetyltransferase (SSAT), a polyamine metabolic enzyme. Furthermore, treatment with TS siRNA delivered by atelocollagen showed a significant cytostatic effect through the induction of apoptosis in a xenograft model.</p> <p>Conclusion</p> <p>TS may be an important therapeutic target and siRNA targeting TS may be of potential therapeutic value in ACC.</p

Gene Expression Signature Analysis Identifies Vorinostat as a Candidate Therapy for Gastric Cancer

Gastric cancer continues to be one of the deadliest cancers in the world and therefore identification of new drugs targeting this type of cancer is thus of significant importance. The purpose of this study was to identify and validate a therapeutic agent which might improve the outcomes for gastric cancer patients in the future. manifested a reversed pattern.We showed that analysis of gene expression signature may represent an emerging approach to discover therapeutic agents for gastric cancer, such as vorinostat. The observation of altered gene expression after vorinostat treatment may provide the clue to identify the molecular mechanism of vorinostat and those patients likely to benefit from vorinostat treatment

Low expression of gamma-glutamyl hydrolase mRNA in primary colorectal cancer with the CpG island methylator phenotype

The CpG island methylator phenotype (CIMP+) in colorectal cancer (CRC) is defined as concomitant and frequent hypermethylation of CpG islands within gene promoter regions. We previously demonstrated that CIMP+ was associated with elevated concentrations of folate intermediates in tumour tissues. In the present study, we investigated whether CIMP+ was associated with a specific mRNA expression pattern for folate- and nucleotide-metabolising enzymes. An exploratory study was conducted on 114 CRC samples from Australia. mRNA levels for 17 genes involved in folate and nucleotide metabolism were measured by real-time RT-PCR. CIMP+ was determined by real-time methylation-specific PCR and compared to mRNA expression. Candidate genes showing association with CIMP+ were further investigated in a replication cohort of 150 CRC samples from Japan. In the exploratory study, low expression of γ-glutamyl hydrolase (GGH) was strongly associated with CIMP+ and CIMP+-related clinicopathological and molecular features. Trends for inverse association between GGH expression and the concentration of folate intermediates were also observed. Analysis of the replication cohort confirmed that GGH expression was significantly lower in CIMP+ CRC. Promoter hypermethylation of GGH was observed in only 5.6% (1 out of 18) CIMP+ tumours and could not account for the low expression level of this gene. CIMP+ CRC is associated with low expression of GGH, suggesting involvement of the folate pathway in the development and/or progression of this phenotype. Further studies of folate metabolism in CIMP+ CRC may help to elucidate the aetiology of these tumours and to predict their response to anti-folates and 5-fluorouracil/leucovorin.K. Kawakami, A. Ooyama, A. Ruszkiewicz, M. Jin, G. Watanabe, J. Moore, T. Oka, B. Iacopetta and T. Minamot